FDA OKs First Drug for Symptoms of Rare Liver Disease in Kids

The FDA approved odevixibat (Bylvay) for treating young children with intense itching caused by progressive familial intrahepatic cholestasis (PFIC), manufacturer Albireo Pharma announced on Tuesday.

Odevixibat becomes the first therapy for the rare disease and was approved to treat pruritus in all PFIC subtypes for patients ages 3 months and older. It was described as a “potent, non-systemic ileal bile acid transport inhibitor” that is administered daily by opening a capsule and sprinkling the contents on soft foods. The FDA drug label noted the drug should be taken in the morning with a meal and the capsules should not be crushed or chewed.

PFIC is an inherited disease caused by certain gene mutations that appears within the first few months of life, according to the FDA. It affects an estimated 1 to 2 people per 100,000. Increased levels of bile acids in the body and skin may cause pruritus, or intense itching, resulting in bleeding, excoriations, scars, and disrupt sleep, the agency noted.

The disease can progress to cirrhosis and liver failure within 10 years, the manufacturer said. Until now, patients required biliary diversion surgery or liver transplantation in order to live past age 30.

Approval was based on findings from the phase III PEDFIC 1 trial, and an open-label extension study, PEDFIC 2.

“Treating children with PFIC can be difficult and frustrating given the current treatment options. Bylvay gives us a non-surgical option,” said investigator Richard Thompson, PhD, of King’s College London in England, in a statement.

In PEDFIC 1, 62 patients ages 6 months to 16 years were randomized 2:1 to receive odevixibat or placebo daily for 24 weeks. The trial met its primary endpoint, with a significant difference in positive pruritus assessments compared to placebo (53.3% vs 28.7%, respectively; P=0.004), and was well-tolerated, with 9.5% of patients in the intervention group reporting diarrhea or frequent bowel movements compared to 5.0% in the placebo group.

PEDFIC 2 found patients showed “sustained reductions in serum bile acids as well as improvements in pruritus assessments, growth and other markers of liver function” for up to 48 weeks, the manufacturer said.

In addition to diarrhea, the drug label noted liver test abnormalities, saying clinicians should obtain baseline liver tests, and reduce or interrupt dosing if abnormalities occur. Persistent abnormalities could merit discontinuation. Clinicians should also monitor for fat-soluble vitamin deficiency. Other common adverse reactions included abdominal pain and vomiting.

Albireo said odevixibat is also being studied in other rare pediatric cholestatic liver diseases, such as Alagille syndrome and biliary atresia. Topline data from these studies is expected in 2022 and 2024, respectively.